Humanized antibodies specific for HSP65-derived peptide-6 methods and uses thereof
AssigneeProtab Ltd.
InventorsYaakov Naparstek, Shira Yair
Life of this patent
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Abstract
The present invention relates to humanized antibodies that specifically bind a polypeptide comprising peptide-6 as denoted by SEQ ID NO. 15, that is an HSP65 derived peptide. More specifically, the invention relates to humanized anti-peptide-6 antibodies, compositions, methods and uses thereof for the treatment of immune-related disorders, specifically, inflammatory disorders such as arthritis, IBD, psoriasis, diabetes and MS. The invention further provides combined compositions and kit combining the humanized antibodies of the invention and at least one anti-inflammatory agent, as well as uses of the humanized antibodies in diagnostic kits and methods.
Claims21
A humanized antibody or any antigen-binding fragment thereof that specifically binds a polypeptide comprising SEQ ID NO:
- 15, the humanized antibody comprising:
- a) a heavy chain variable region which comprising an amino Acid sequence which is at least about 70% identical to SEQ ID NO. 1, said heavy chain variable region comprising Cys at position H22, Ser at H23, Gly at H26, Phe at H27, Ser at H28, Leu at H29, Ser at H30, Thr at H31, Ser at H32, Asn at H33, Met at H34, Gly at H35, Val at H35A, Gly at H35B, Leu at H48, His at H50, Ile at H51, Leu at H52, Trp at H53, Asn at H54, Asp at H55, Ser at H56, Lys at H57, Tyr at H58, Tyr at H59, Asn at H60, Pro at H61, Ala at H62, Leu at H63, Lys at H64, Ser at H65, Cys at H92, Met at H95, Gly at H96, Gly at H97, Tyr at H98, Tyr at H99, Gly at H100, Asn at H100A, Tyr at H100B, Gly at H100C, Tyr at H100D, Tyr at H100E, Ala at H100F, Met at H100G, Asp at H101 and Tyr at H102, and, optionally, at least one of Leu at H49, Tyr at H74, Ile at H11, Ser at H41 and Ser at H108;
- and
- b) a light chain variable region which comprising an amino Acid sequence which is at least about 70% identical to SEQ ID NO. 2, said light chain variable region comprising Gln at position L1, Cys at L23, Thr at L24, Ala at L25, Ser at L26, Ser at L27, Ser at L27A, Val at L28, Ser at L29, Ser at L30, Ser at L31, Tyr at L32, Leu at L33, His at L34, Trp at L47, Ser at L50, Thr at L51, Ser at L52, Asn at L53, Leu at L54, Ala at L55, Ser at L56, Tyr at L71, Cys at L88, His at L89, Gln at L90, Tyr at L91, His at L92, Arg at L93, Ser at L94, Pro at L95, Pro at L96 and Thr at L97 and optionally at least one of Met at L21, Ile at L10 and Ala at L80;
- wherein the positions are determined according to the Kabat numbering system.
A chimeric monoclonal antibody that specifically binds a polypeptide comprising SEQ ID NO:
- 15, wherein said antibody comprises a human immunoglobulin constant region and a murine immunoglobulin variable region, said variable region comprising a light chain variable region having the amino acid sequence as denoted by SEQ ID NO. 2 and a heavy chain variable region having the amino acid sequence as denoted by SEQ ID NO. 1.
A composition comprising a pharmaceutically acceptable carrier, excipient or diluent, and, as an active ingredient, an effective amount of at least one humanized antibody or antigen-binding fragment thereof that specifically binds a polypeptide comprising SEQ ID NO:
- 15, the humanized antibody comprising:
- a) a heavy chain variable region comprising an amino acid sequence which is at least about 70% identical to SEQ ID NO. 1, said heavy chain variable region comprising Cys at position H22, Ser at H23, Gly at H26, Phe at H27, Ser at H28, Leu at H29, Ser at H30, Thr at H31, Ser at H32, Asn at H33, Met at H34, Gly at H35, Val at H35A, Gly at H35B, Leu at H48, His at HSO, Ile at H51, Leu at H52, Trp at H53, Asn at H54, Asp at H55, Ser at H56, Lys at H57, Tyr at H58, Tyr at H59, Asn at H60, Pro at H61, Ala at H62, Leu at H63, Lys at H64, Ser at H65, Cys at H92, Met at H95, Gly at H96, Gly at H97, Tyr at H98, Tyr at H99, Gly at H100, Asn at H100A, Tyr at H100B, Gly at H100C, Tyr at H100D, Tyr at H100E, Ala at H100F, Met at H100G, Asp at H101 and Tyr at H102, and, optionally, at least one of Leu at H49, Tyr at H74, Ile at H11, Ser at H41 and Ser at H108;
- and
- b) a light chain variable region comprising an amino acid sequence which is at least about 70% identical to SEQ ID NO. 2, said light chain variable region comprising Gln at position L1, Cys at L23, Thr at L24, Ala at L25, Ser at L26, Ser at L27, Ser at L27A, Val at L28, Ser at L29, Ser at L30, Ser at L31, Tyr at L32, Leu at L33, His at L34, Trp at L47, Ser at L50, Thr at L51, Ser at L52, Asn at L53, Leu at L54, Ala at L55, Ser at L56, Tyr at L71, Cys at L88, His at L89, Gln at L90, Tyr at L91, His at L92, Arg at L93, Ser at L94, Pro at L95, Pro at L96 and Thr at L97 and, optionally, at least one of Met at L21, Ile at L10 and Ala at L80;
- wherein the positions are determined according to the Kabat numbering system.
A method for the treatment or amelioration of an immune-related disorder, wherein said disorder is an inflammatory bowel disease (IBD) or arthritis, said method comprising the step of administering to a subject in need thereof a therapeutically effective amount of at least one humanized antibody or antigen-binding fragment thereof that specifically binds a polypeptide comprising SEQ ID NO:
- 15, or of a composition comprising the same, wherein said humanized antibody comprises:
- a) a heavy chain variable region comprising an amino acid sequence which is at least about 70% identical to SEQ ID NO. 1, said heavy chain variable region comprising Cys at position H22, Ser at H23, Gly at H26, Phe at H27, Ser at H28, Leu at H29, Ser at H30, Thr at H31, Ser at H32, Asn at H33, Met at H34, Gly at H35, Val at H35A, Gly at H35B, Leu at H48, His at HSO, Ile at H51, Leu at H52, Trp at H53, Asn at H54, Asp at H55, Ser at H56, Lys at H57, Tyr at H58, Tyr at H59, Asn at H60, Pro at H61, Ala at H62, Leu at H63, Lys at H64, Ser at H65, Cys at H92, Met at H95, Gly at H96, Gly at H97, Tyr at H98, Tyr at H99, Gly at H100, Asn at H100A, Tyr at H100B, Gly at H100C, Tyr at H100D, Tyr at H100E, Ala at H100F, Met at H100G, Asp at H101 and Tyr at H102, and, optionally, at least one of Leu at H49, Tyr at H74, Ile at H11, Ser at H41 and Ser at H108;
- and
- b) a light chain variable region comprising an amino acid sequence which is at least about 70% identical to SEQ ID NO. 2, said light chain variable region comprising Gln at position L1, Cys at L23, Thr at L24, Ala at L25, Ser at L26, Ser at L27, Ser at L27A, Val at L28, Ser at L29, Ser at L30, Ser at L31, Tyr at L32, Leu at L33, His at L34, Trp at L47, Ser at L50, Thr at L51, Ser at L52, Asn at L53, Leu at L54, Ala at L55, Ser at L56, Tyr at L71, Cys at L88, His at L89, Gln at L90, Tyr at L91, His at L92, Arg at L93, Ser at L94, Pro at L95, Pro at L96 and Thr at L97 and, optionally, at least one of Met at L21, Ile at L10 and Ala at L80;
- wherein the positions are determined according to the Kabat numbering system.
Dependencies are inferred from the claim text.